ISSN 2415-3060 (print), ISSN 2522-4972 (online)
JMBS
  • 37 of 59
Up
JMBS 2016, 1(1): 178–181
https://doi.org/10.26693/jmbs01.01.178
Biology

α-2-Macroglobulin Activity at Pothology (Depression, Alcoholism, Hipotension)

Lomako V.V.1, Samokhina L.M.2, Somova K.V.3
Abstract

α-2-macroglobulin (α-2-MG) is one of the main regulators of intercellular relationships and is synthesized by virtually all cells (hepatocytes, hematopoietic cells, fibroblasts, myocytes, epithelial and nerve cells). It is shown that macroglobulin is capable of forming complexes with almost all currently known proteases regardless of their origin. α-2-MG is one of the main factors that contributes to the binding of foreign antigens by the immune system cells and forms complexes with nearly all currently known proteases, independent of their origin. The role of α-2-MG in the development of pathological processes continues to be actively explored today. α-2-MG activity was determined in tissue samples (serum, cerebral cortex, hypothalamus, heart, lungs, liver and kidneys) of intact rats (7-8 months and 17-18 months) and in rats on the background of pathological states development (depression, alcoholism and hypotension) by a highly sensitive enzymatic method. Depression was simulated by the stress of “not-avoiding” in an isolated chamber, which contributed to the development of the pathological symptom complex in animals ("learned helplessness"); hypotension was achieved by injections of 2.5% of chlorpromazine; "two bottle choice method" was used for alcoholisation during 10 months. Control I - 7-8 months rats; control II - 17-18 months rats. Blood pressure (BP) was recorded by tonometer, the cuff was put on a tail. Depression was accompanied by hypertension with higher blood pressure (221.6 ± 9.8 mmHg, in the control I - 100.8 ± 6.6 mmHg) than alcoholism (176,7 ± 20 68 mm Hg, in the control II - 130,00 ± 12,25 mmHg); blood pressure increases with age; at hypotension BP was reduced by 35 ± 5 mmHg. At depression the α-2-MG activity significantly (by one order of magnitude) increased in all tissues except the brain cortex (unchanged); in young animals control was much lower than that of old ones (all tissues). Alcoholisation reduced the α-2-MG activity dramatically, particularly in the hypothalamus, the lungs, heart and kidneys (by two orders of magnitude) in the other samples - 6-10 times. The α-2-MG activity in hypotensive rats was reduced in 10 times in all tissues except the blood serum (increased). The activity of α-2-MG increases with age and its dramatic increase at depression is also in agreement with the ideas that the depressive like states are evolved precisely on the background of the immune system activation. Alcohol has negative impacts at all the links of immunity. Since macroglobulins play a significant role in the humoral and cellular immune responses, the observed changes in the activity of α-2-MG may indicate both the activation and the suppression of the immune system in the development of pathology. Excess α-2-MG created by complexation with proteases, promotes apoptosis of damaged cells, promotes phagocytosis activity regulation by the cytokines and is aimed at localization of necrosis focus. Thus, fluctuations in the α-2-MG activity faithfully reflect age-dependent and pathologic changes in the state of immunity.

Keywords: α-2-macroglobulin, depression, alcoholism, hypertension, hypotension, age

Full text: PDF (Rus) 128K

References
  1. Anischenko TG, Semyachkina-Glushkovskaya OV, Berdnikova VA, Sindyakova TA. Vliyanie vozrasta i pola na pokazateli arterialnogo davleniya, razvitie pochechnoy gipertenzii i soderzhanie oksida azota v krovi belyih kryis. Byull eksperim biol med. 2010; 149 (1): 4-6.
  2. Zorin NA, Zorina VN, Zorina RM. Universalnyiy modulyator tsitokinov α-2- makroglobulin (Obzor literaturyi). Immunologiya. 2004; 25 (5): 302-4.
  3. Iskandarova LR, Haybulina NG, Amirova AR, Mutalova EG. Pokazateli mezhkletochnyih molekul adgezii, immunnoy sistemyi pri arterialnoy gipertonii. Sovremennyie naukoemkie tehnologii. 2005; 10: 43-4.
  4. Hadartsev AA, Morozov VN, Hrupachev AG, i dr. Depressiya antistressovyih mehanizmov kak osnova razvitiya patologicheskogo protsessa. Fundament issledovaniya. 2012; 4: 371-5.
  5. Armstrong PB, Quigley JP. Alpha2-macroglobulin: an evolutionarily conserved arm of the innate immune system. Dev Comp Immunol. 1999; 23: 375-90. https://doi.org/10.1016/S0145-305X(99)00018-X
  6. Bapat PR, Satav AR, Husain AA, Seema D. Shekhawat, Anuja P Kawle, Justin J Chu, Hemant J Purohit, Hatim F Daginawala, Girdhar M Taori, Rajpal S Kashyap. Differential Levels of Alpha-2-Macroglobulin, Haptoglobin and Sero-Transferrin as Adjunct Markers for TB Diagnosis and Disease Progression in the Malnourished Tribal Population of Melghat, India. PLoS One. 2015; 10 (8). https://doi.org/10.1371/journal.pone.0133928
  7. Birkenmeier G. Targeting the Proteinase Inhibitor and Immune Modulatory Function of Human α2-Macroglobulin. Mod Asp Immunobiol. 2001; 2 (1): 32-6.
  8. Federici Canova D, Pavlov AM, Norling LV, et al. Alpha-2-macroglobulin loaded microcapsules enhance human leukocyte functions and innate immune response. J Control Release. 2015; 217 (10): 284-92. https://doi.org/10.1016/j.jconrel.2015.09.021.
  9. Fujita T, Nagayama A, Anazawa S. Circulating alpha-2-macroglobulin levels and depression scores in patients who underwent abdominal cancer surgery. J Surg Res. 2003; 114 (1): 90-4. https://doi.org/10.1016/S0022-4804(03)00194-X
  10. Lysiak J. α2-Мacroglobulin functions as a cytokine carrier to induce nitric oxide synthesis and cause nitric oxide-dependent cytotoxity in the RAW 264.7 macrophage cell line. J Biol Chem. 1995; 270: 21919-27.
  11. Maeda H, Akaike T, Wu J, et al. Bradikinin and nitric oxide in infectious disease and cancer. Immunopharmacology. 1996;33:222-30.https://doi.org/10.1016/0162-3109(96)00063-X
  12. Nezu T, Hosomi N, Aoki S, Deguchi K, Masugata H, Ichihara N, Ohyama H, Ohtsuki T, Kohno M, Matsumoto M. Alpha2-macroglobulin as a promising biomarker for cerebral small vessel disease in acute ischemic stroke patients. J Neurol. 2013; 260 (1): 2642-9. https://doi.org/10.1007/s00415-013-7040-x
  13. Romeo J, Warnberg J, Nova E, Díaz LE, Gómez-Martinez S, Marcos A. Moderate alcohol consumption and the immune system: A review. British Journal of Nutrition. 2007; 98 (1): S111-5. https://doi.org/10.1017/S0007114507838049
  14. Thieme R, Kurz S, Kolb M, Tewodros Debebe, Susanne Holtze, Michaela Morhart, Klaus Huse, Karol Szafranski, Matthias Platzer, Thomas B. Hildebrandt, Gerd Birkenmeier. . Analysis of Alpha-2 Macroglobulin from the Long-Lived and Cancer-Resistant Naked Mole-Rat and Human Plasma. PLoS One. 2015; 10 (6): e0130470. https://doi.org/10.1371/journal.pone.0130470
  15. Tsiouris JA. Metabolic depression in hibernation and major depression: An explanatory theory and an animal model of depression. Med Hypotheses. 2005; 65 (5): 829-40. https://doi.org/10.1016/j.mehy.2005.05.044